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. 2024 May 7:15:1331282.
doi: 10.3389/fendo.2024.1331282. eCollection 2024.

Increased Vasoactive Intestinal Peptide (VIP) in polycystic ovary syndrome patients undergoing IVF

Luana Sallicandro  1   2 , Elko Gliozheni  1   2 , Davide Feudi  1 , Paola Sabbatini  2 , Roberto Maria Pellegrino  1 , Husam B R Alabed  1 , Domenico Baldini  3 , Sandro Gerli  2   4 , Carlo Alviggi  5 , Eliano Cascardi  6 , Ettore Cicinelli  7 , Antonio Malvasi  7 , Bernard Fioretti  1   4
Affiliations

Increased Vasoactive Intestinal Peptide (VIP) in polycystic ovary syndrome patients undergoing IVF

Luana Sallicandro et al. Front Endocrinol (Lausanne). .

Abstract

Introduction: Polycystic ovary syndrome (PCOS) is a common multifactorial and polygenic disorder of the endocrine system, affecting up to 20% of women in reproductive age with a still unknown etiology. Follicular fluid (FF) represents an environment for the normal development of follicles rich in metabolites, hormones and neurotransmitters, but in some instances of PCOS the composition can be different. Vasoactive intestinal peptide (VIP) is an endogenous autonomic neuropeptide involved in follicular atresia, granulosa cell physiology and steroidogenesis.

Methods: ELISA assays were performed to measure VIP and estradiol levels in human follicular fluids, while AMH, FSH, LH, estradiol and progesterone in the plasma were quantified by chemiluminescence. UHPLC/QTOF was used to perform the untargeted metabolomic analysis.

Results: Our ELISA and metabolomic results show: i) an increased concentration of VIP in follicular fluid of PCOS patients (n=9) of about 30% with respect to control group (n=10) (132 ± 28 pg/ml versus 103 ± 26 pg/ml, p=0,03) in women undergoing in vitro fertilization (IVF), ii) a linear positive correlation (p=0.05, r=0.45) between VIP concentration and serum Anti-Müllerian Hormone (AMH) concentration and iii) a linear negative correlation between VIP and noradrenaline metabolism. No correlation between VIP and estradiol (E2) concentration in follicular fluid was found. A negative correlation was found between VIP and noradrenaline metabolite 3,4-dihydroxyphenylglycolaldehyde (DOPGAL) in follicular fluids.

Conclusion: VIP concentration in follicular fluids was increased in PCOS patients and a correlation was found with noradrenaline metabolism indicating a possible dysregulation of the sympathetic reflex in the ovarian follicles. The functional role of VIP as noradrenergic modulator in ovarian physiology and PCOS pathophysiology was discussed.

Keywords: In Vitro Fertilization (IVF); PCOS (polycystic ovarian syndrome); VIP (vasoactive intestinal peptide); follicular fluid; metabolomic; noradrenalin (NA); ovarian innervation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
VIP levels are increased in the PCOS group. (A) Scatter plot of VIP concentration on follicular fluid in control (gray) and PCOS (red) patients. The contingency table represented in the bottom divide the PCOS and CTRL samples into two populations by using a threshold of 150 pg/ml (Fisher’s exact test=0.03). (B) Relationship between anti-Müllerian hormone (AMH) serum level and VIP level in follicular fluid. The dash line represents the best linear fit (p=0.053) with a correlation index of 0.45. (*) indicates the significance with p< 0,05.
Figure 2
Figure 2
E2 levels are are not correlated with VIP concentration. (A) Scatter plot of E2 concentration on follicular fluid in control (gray) and PCOS (red) patients. (B) Relationship between E2 and VIP levels in follicular fluid. To be noted the absence of correlation between VIP and E2. (*) indicates the significance with p< 0,05.
Figure 3
Figure 3
Metabolic analysis of follicular fluid. (A) Exemplificative spectral peak collection of follicular fluid obtained from a control patient. Different colours represent different metabolites AU=arbitrary units. (B) Average scatter Volcano plot displaying all metabolites dispersed based on the fold change (FC) and p-value. The dashed line represents p=0.05, with blue and red dots indicating down-regulated and up-regulated metabolites, respectively.
Figure 4
Figure 4
Metabolomics Pathway Analysis of Differential Metabolites in Follicular Fluid Between Normal and PCOS Patients. (A) Pathway analysis results of the 137 named metabolites. The square box indicates the pathway related to catecholaminergic metabolites (Tyrosine metabolites). (B) Comparation of dopamine concentration between control and PCOS group (no significance found p=0.50). (C) Scatter plot of noradrenergic metabolites (DOPGAL) versus VIP levels. The dashed line represents the linear correlation with the data. The empty square data points represent outlier data not included in linear regression. The grey and red dots indicate normal and PCOS patients, respectively.
Figure 5
Figure 5
Hypothetic mechanism of VIP dysregulation in the PCOS disorder. In normal conditions (left picture) the NA sympathetic fibers release NA that is involved in correct folliculogenesis. In the PCOS condition (right picture) VIP, derived from autonomic (sympathetic and parasympathetic) or from sensory neurons, inhibits NA release thus modifing the normal folliculogenesis. This inhibition nullifies the increased excitability originated from the increase of density and of eccitability of sympathetic system in the PCOS ovary. Figure created with BioRender.com.
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References

    1. Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol. (2018) 14:270–84. doi: 10.1038/nrendo.2018.24 - DOI - PubMed
    1. Lizneva D, Suturina L, Walker W, Brakta S, Gavrilova-Jordan L, Azziz R. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril. (2016) 106:6–15. doi: 10.1016/j.fertnstert.2016.05.003 - DOI - PubMed
    1. van der Ham K, Louwers YV, Laven JSE. Cardiometabolic biomarkers in women with polycystic ovary syndrome. Fertil Steril. (2022) 117:887–96. doi: 10.1016/j.fertnstert.2022.03.008 - DOI - PubMed
    1. Guastella E, Longo RA, Carmina E. Clinical and endocrine characteristics of the main polycystic ovary syndrome phenotypes. Fertil Steril. (2010) 94:2197–201. doi: 10.1016/j.fertnstert.2010.02.014 - DOI - PubMed
    1. Vink JM, Sadrzadeh S, Lambalk CB, Boomsma DI. Heritability of polycystic ovary syndrome in a Dutch twin-family study. J Clin Endocrinol Metab. (2006) 91:2100–4. doi: 10.1210/jc.2005-1494 - DOI - PubMed